Imaginary pills and open-label placebos can reduce test anxiety by means of placebo mechanisms

Placebos have been shown to be beneficial for various conditions even if administered with full transparency. Hence, so-called open-label placebos (OLPs) offer a new way to harness placebo effects ethically. To take this concept one step further, this study aimed at evaluating placebo effects without the use of a physical placebo, i.e., by imagining taking a pill. Healthy students (N = 173) with self-reported test anxiety were either randomized to an imaginary pill (IP; n = 55), an OLP (n = 59) or a control group (CG; n = 59). Both intervention groups were instructed to take two pills daily for three weeks. Primary outcome was test anxiety, secondary outcomes were sleep quality, general well-being and test performance. Groups test anxiety differed at study-endpoint, F(2,169) = 11.50, p < .001. Test anxiety was lower in the intervention groups compared to the CG, t(169) = − 4.44, p < .001, d = − 0.71. The interventions did not differ significantly, i.e., both were similarly efficacious, t(169) = 0.61, p = .540, d = 0.11. The interaction between group and time in explaining test anxiety was significant, F(5,407.93) = 6.13, p < .001. OLPs and IPs reduced test anxiety in healthy participants compared to the CG. This finding opens the door for a novel and ethical method to harness placebo effects.


Identifying the OLP-sensitive problem
Before I explain the concept of the open administration of placebos and how we use these placebo effects with the imaginary pill intervention, I would like to know more about your test anxiety and your preparation stress. Could you use a previous exam situation to describe what the symptoms feel like? I ask you now to think back to that bad exam/situation. Can you now describe to me, based on this previous exam situation, what the symptoms of your exam anxiety felt like? What are the sensations in your body? What are your thoughts and emotions when you experience this anxiety? Now, thinking of the upcoming exam, if you had to specify how strong these symptoms are from 0-10 (not at all -very strong) in this moment, what would you say? And now can you describe how you would like to feel in your exam phase/during the exam? Can you describe to me a specific situation where you feel this? What are your feelings in this situation?

Explaining importance of group
As you already know from the study information, we randomly assign all study participants to one of the three study groups. You have been assigned to the control group, which means you will not receive a treatment. This group and your participation is very important for our study. Only through the control group can we see how symptoms naturally behave when you do not receive a treatment. So, we are also asking you to fill out all the online surveys accordingly. You will still receive weekly surveys.

Building trust in the treatment
Is it ok if I now explain the concept of open-label placebos and how you can use this placebo effect with the imaginary pill for your goal -the positive experience, we've just talked about? OK, we know from clinical research that placebos have significant effects on pain, depression and anxiety and that these effects can even be demonstrated in changes in brain activity and the release of neurotransmitters. As mentioned earlier, scientists previously assumed that placebo pills can only help if they are given covertly, i.e. with deception. Now, however, more recent studies suggest that this is not the case. This means that placebos can work even if the patient knows that it is a placebo. We are incorporating this approach in our study. Many double-blind randomized studies show that the placebo effect is very effective for many complaints. This means that placebos can relieve pain, cramps and gastrointestinal complaints, among other problems, and also have a very positive effect on mood. Especially for chronic back pain and irritable bowel syndrome, the openlabel placebo treatment has been shown to be very effective, even in patients where nothing else has worked. Here at the division, a study has already been carried out in which a placebo cream was

Deceptive and OLPs are effective
We know from clinical research that placebos have significant effects on pain, depression and anxiety and that these effects can even be demonstrated in changes in brain activity and the release of neurotransmitters. As mentioned earlier, scientists previously assumed that placebo pills can only help if they are given covertly, i.e. with deception. Now, however, more recent studies suggest that this is not the case. This means that placebos can work even if the patient knows that it is a placebo. We are incorporating this approach in our study. Many double-blind randomized studies show that the placebo effect is very effective for many complaints. This means that placebos can relieve pain, cramps and gastrointestinal complaints, among other problems, and also have a very positive effect on mood. Especially for chronic back pain and irritable bowel syndrome, the openlabel placebo treatment has been shown to be very effective, even in patients where nothing else has worked. Here at the division, a study has already been carried out in which a placebo cream was used for the treatment of heat-induced pain. And there too we found large placebo effects. A positive placebo effect has also been shown for test anxiety. This has been shown recently by a

Nature of exam
In your case, we would be interested in how the exam stress and anxiety manifests itself and what your general learning strategies are. I will possibly make some notes on this. Before we get to your exam anxiety itself, I'd like to ask you questions about the nature of the exam: -What format does the exam take? Is it written or oral? -Are you generally more afraid of written/oral (repeat what was said) exams, compared to exams that have a different format? -Is it a repetition exam? -If not yet clear: Does the test anxiety also have to do with the subject in which the exam takes place? In which subject is the exam? What does this subject involve? -What makes the exam so difficult or scary for you? -How often are you afraid of an exam to this extent or are you stressed because of the exam (in every learning phase or especially now)? (Possibly why especially now?) used for the treatment of heat-induced pain. And there too we found large placebo effects. A positive placebo effect has also been shown for test anxiety. This has been shown recently by a study from Germany, where they tested open placebos also in students.
We are now considering the possibility that if placebos work, even though we know that they are placebos, then we could simply omit the sugar pill and imagine the pill and still have all the placebo effects. A reaction to placebos is not only triggered by the placebo pill itself, but also by the imaginative meaning that is both consciously and automatically attributed to the placebo pill. Imagination research shows, for example, that the idea of something activates the same areas of the brain as when one actually sees or experiences something. A study has also shown that the idea of exercising in a gym can already lead to muscle growth. Accordingly, it is possible to imagine taking this pill and achieve a similar effect as if you were taking a real pill. And this is exactly what I would like to discuss and practice with you. Okay for you? study from Germany, where they tested open placebos also in students.

Constructing a personally meaningful pill
The first step is to find an imaginary pill for you.

An open attitude towards the treatment can be helpful but is not necessary
It's also absolutely okay if you have doubts that placebos work. As mentioned before, placebos can work automatically, which means they can work even if you have doubts.

Learning strategies
-Now I'm still wondering what your general learning strategies are: Do you work in study groups or more alone or both? -Do you study with summaries, mind maps, study plans or flashcards? Thank you very much for your answers to the many questions, it is very informative.
Swallow the pill slowly. Now it is in your body and starts to work. Maybe you can already feel the effects of the pill. Try to feel what the pill does to you. Maybe the pill has also other effects, such as making your mouth dry. You might get warm or a little dizzy. You have now had your first experience of such an imaginary pill taking. Try to remember this state so that you can recall it on your own. Now, if you had to indicate again after taking your imaginary pill how strong at the moment your symptoms are from 0-10 when you think about the upcoming exam, what would you say?

Suggestions for self-administering in real life and building adherence
For the effect of this intervention, it is now important that you take such an imaginary pill twice a day from the time when you receive a reminder per e-mail: once in the morning and once in the evening, in order to reach the desired state (up to the exam). Before taking the pill, take a little time to recall the image of the pill you have just described. I also ask you to fill out the announced surveys once a week until the exam. You will receive an email with the link at the right time, so that you remember to do it. Then one more thing: In order for us to really be able to identify what the effects of an imaginary pill are, we ask you not to take sweets like Sugus or Tiktak to make it easier for you to imagine. As said before, it is best to simply take your time and take the imaginary pill twice a day for three weeks.

Taking the pill faithfully is important
Therefore, it is important that you take the placebos regularly and according to the prescription. This means for you that you have to take the placebo pills faithfully in order to feel an effect. It is important for you to know that for some people the effects occur earlier and for others later. When you take the pills, we recommend that you also be aware of what the pills are supposed to help you against, i.e., to achieve the positive state you described earlier. I am aware that this may sound unfamiliar to you at first. However, we want to find out what happens to your symptoms when you take placebo pills every day. Therefore, I would like to encourage you to give the open placebo treatment a chance and see what happens. Now you may open the parcel and take out the box with the placebo pills in it. Please take two pills every day for the next three weeks (until the exam) from the time you receive a reminder by e-mail. It We will also send you daily reminders that you are reminded to take the imaginary pill. I am aware that the concept of the imaginary pill may sound strange to you at first. But we would like to find out whether you can reach the desired state if you imagine taking a pill every day to relieve your test anxiety. We have developed this procedure here at the university in collaboration with experts from all over the world and we really believe in the effectiveness of this treatment. Also, because there are already several cases from the clinic where the imaginary pill treatment has shown very good effectiveness. Therefore, I would like to encourage you to give the imaginary pill a chance and see what happens.
is best to take the pills at the same time in the morning and in the evening. There is also a small envelope in the package, which you can open right away. On the envelope you will find information on how to take the pills. As we said, we will send you daily reminders to remember to take your pills. If you take two pills a day for three weeks, that's a total of 42 pills. There are 50 pills in the package, which means there are 8 pills too many. You don't have to send them back to us (you can take them at a later date, for example). During the three weeks please take always two pills per day and not more or less. I also ask you to fill out the announced surveys once a week until the exam. You will receive an email with the link at the right time to make sure you remember to do this.